The handling, mixing and delivery of bulk solids present unique difficulties when the solids are handled in powdered form. Often, one or more physical properties of the powdered particulates themselves are important, or even critical, to the application for which the composition is intended. Particulate shape, particulate size and particulate porosity often describe important physical properties or characteristics. Environmental conditions (humidity, temperature, shear forces among others) encountered by a powder during use or storage can and often do affect one or more properties of the particulates. Aggregation, agglomeration, attrition and flocculation represent the most common degradative effects on a powder and their presence or progression greatly limits the utility and viability of many powder compositions.
Achieving a uniform blend of dry bulk solids is a problem faced daily by engineers and operators in industries as varied as pharmaceuticals, foods, plastics and battery production. Even when an acceptable blend is obtained additional challenges arise in maintaining the blend through one or more pieces of downstream equipment. Poor blending or the inability to maintain an adequate blend before and during processing lead to additional and unnecessary costs, including costs associated with rejected material and decreased yields, added blending time and energy, decreased productivities, start-up delays and defective or out-of-specification products. Powder caking of raw and in-process materials, particularly during storage (m, e.g., bags or drums) can also pose significant problems. Both powder caking and an inability to achieve uniform blends and mixtures can decrease batch uniformity which, among other drawbacks, can require increased testing and sampling. In pharmaceutical applications, batch nonuniformities translate directly to dose nonuniformities.
Some flowability aids are known. Fumed silica, for example, is one popular powder additive that can be used to improve flow characteristics. While relatively inexpensive, fumed silica often is ineffective in preventing agglomeration of many particle types. Flowability is also a matter of degree; many, if not most, uses of fumed silica lead to some agglomeration and aggregation. Some undemanding industrial applications can tolerate a level of agglomeration not tolerated in more demanding applications. Applications involving precise metering or mixing of a powder, however, require more. Even in relatively undemanding applications the ability to improve powder flow can provide an increase in homogeneity with milder mixing conditions or with reduced mixing periods. Additionally, increased powder flowabilities can allow utilization of lower levels of expensive ingredients, e.g., dyes and pigments, particularly where the requirement of using a level of such ingredients correlates with the dispersibility of the materials in the powder with which they are mixed.
The preparation or delivery of pharmaceuticals and medicaments as powders is particularly demanding. Pharmaceutical applications must take careful account of various particle or powder characteristics, and pharmaceutical compositions often are prepared as powders as an intermediate step to final formulation in myriad forms for delivery to the patient. Pharmaceutical compositions can be tableted or encapsulated for oral gastro-intestinal ingestion and delivery. They also can be incorporated into a dry powder inhaler for delivery to the respiratory tract. The ability to achieve homogenous blends of compositions containing relatively low levels (by weight) of pharmaceutically active ingredients is very difficult.
Dry powder inhalation of a pharmaceutical or drug composition requires unique and challenging physical property profiles for a powder. In order to efficiently and efficaciously deliver pharmaceutical compositions to the lung in powdered form two competing criteria must be balanced:                1. The drug particles to be delivered must be sufficiently small so that the particles can be inhaled and penetrate into the deep lung. The aerodynamic diameter of the particles (Equation 1 below) primarily influences this behavior, since deposition in the respiratory tract is controlled by a particle's aerodynamic size rather than its physical or geometric shape. Lung deposition improves substantially for particles less than 5 microns in aerodynamic diameter and decreases substantially for particles with effective aerodynamic diameters of greater than 5 microns.        
                              D          aerodynamic                ≅                              D            physical                    ⁢                                    ρ              χ                                                          (        1        )                            where: ρ is the particle density; and                    χ is the shape factor of the particle (χ=1.0 for perfectly spherical particles and χ≧1 for irregular particles)                        2. Drug particles need also to be sufficiently deagglomerated by a dry powder inhaler (“DPI”) device. Large clusters of multiple drug particles will not penetrate into the deep lung as efficiently as single or very small particle clusters. Traditionally, DPIs have utilized complex mechanical systems to ensure deagglomeration of the particulate powder and even then such systems have yielded only partial success. Competing with the desire for decreasing particle size, the flowability and ease of deagglomeration of powders unfortunately improves with increasing particle size. Below 5 microns in effective particle diameter deagglomeration efficiency exhibits a marked decline.        
To balance these competing effects, recent efforts have developed powders for inhalation that are physically large (and thus effectively deagglomerated), yet are aerodynamically small (thus being more respirable). Some such particles, for example, are hollow spherical-like particles with low density but large relative particle size. Others are significantly irregular in shape and physical character. While achieving some degree of balance between penetrability and flowability, powders of such particles, particularly when formulated in lipid/drug matrices for delivery, tend toward an amorphous state and pose potential stability drawbacks. Concerns also arise when inhaling a large amount of the excipients required to form such matrices. Other methods to balance the competing effects have included adsorbing small respirable drug particles onto larger inert particles (e.g., lactose) which act as a carrier for the particles to provide for bulk deagglomeration but which require additional energy to release the drug from the surface of the carrier particle. Such an approach limits the amount of drug that can be delivered, since a substantial amount of the formulation is comprised of pharmaceutically non-active ingredients. Additional concerns surround the preparation of such powders in a homogenous manner and the ability to measure precise amounts of the powder blends in the final delivery vehicles.
Powder handling and processing technologies today lie significantly behind the development pace of companion technologies used in liquid processes, and there remain a great many practical problems handling powders that current methods cannot effectively address. Powder compositions exhibiting enhanced flowability and processability are desired for a wide range of applications including demanding industrial and pharmaceutical uses.